COLONIC MYOELECTRIC ACTIVITY IN THE IRRITABLE BOWEL SYNDROME

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1 GASTROENTEROLOGY 70: , 1976 Copyright 1976 by The Williams & Wilkins Co. Vol. 70, No.3 Printed in U.S.A. COLONIC MYOELECTRIC ACTIVITY IN THE IRRITABLE BOWEL SYNDROME WILLIAM J. SNAPE, JR., M.D., GERALD M. CARLSON, PH.D., AND SIDNEY COHEN, M.D. Gastrointestinal Section, Departments of Medicine and Physiology, University of Pennsylvania, Philadelphia, Pennsylvania Although the irritable bowel syndrome has been characterized as an abnormality in colonic motor activity occurring in response to certain stimuli, the etiology of this abnormality is unclear. The purpose of this study was to compare colonic myoelectric and motor activity in normal subjects and in patients with the irritable bowel syndrome. Myoelectric activity was recorded using a bipolar electrode clipped to the mucosa of the rectal and rectosigmoid areas. Basic electrical rhythm (BER), spike potential activity, and intraluminal pressure were recorded in both groups. Two types of BER were observed. The major component of the BER had a frequency of approximately 6 cycles per min, whereas the minor component had a frequency of approximately 3 cycles per min. Although both types of BER were recorded in the two groups, the slower-frequency BER was increased in the patients with irritable bowel syndrome. The 3 cycles per min activity was present as 44.1 ± 1.3% of the total BER in the irritable bowel syndrome, as compared with 10.0 ± 1.6% in the normal group (P < 0.001). Basal spike potential and motor activity were similar in both groups. Because it had been demonstrated previously that colonic responsiveness to certain stimuli was increased during the slower frequency BER, it is suggested that the abnormalities in colonic motor response reported in the irritable bowel syndrome may be related to this difference in colonic BER. The irritable bowel syndrome denotes a clinical disorder characterized by either diarrhea or constipation which occurs in association with abdominal pain but without demonstrable organic bowel disease. Although this syndrome constitutes one of the major digestive disorders seen by physicians, and is one of the leading causes of work absenteeism due to illness, 1 there is little insight into its pathogenesis or treatment. Most studies suggest that the irritable bowel syndrome is associated with an abnormality in colonic motor function. Abnormal motor activity has been demonstrated in the distal colon in response to emotional stress,2 meals,3 the hormone cholecystokinin,4 or drugs such as prostigmine. 5 The pathophysiological mechanism of this abnormal motor response is unclear. Recent studies, in man 6 - S and in laboratory animals,9-11 have suggested that the mechanism of abnormal bowel function may be more directly assessed by determining colonic myoelectric activity. Myoelectric activity is recorded as two components, the basic electrical rhythm (BER) and spike activity.9 The purpose of this study was Received June 17, Accepted September 10, Address requests for reprints to: Sidney Cohen, M.D., Gastrointestinal Section, Hospital of the University of Pennsylvania, :i400 Spruce Street, Philadelphia, Pennsylvania This work was supported by Research Grant 5 R01 AM from the National Institutes of Health. Dr. Cohen is supported by a Research Career Development Award,.5 K04 AM , from the National Institutes of Health. The authors wish to thank Miss Susan Kocmund for her expert technical assistance and Miss Mary Carroll for secretarial assistance. 326 to compare rectal and rectosigmoid myoelectric activity in normal subjects and in patients with the irritable bowel syndrome. Methods The diagnosis of the irritable bowel syndrome was made in 7 women and 5 men (23 to 69 years of age), The patients haq either chronic diarrhea, constipation, or a combination of both symptoms lasting longer than 3 months. They had unexplained abdominal pain which was either related or unrelated to meals. All patients had a normal sigmoidoscopic examination and normal upper and lower gastrointestinal tract barium studies. No patient had lactose intolerance or intestinal parasites. All patients were symptomatic at the time of the study. Three women and 7 men (21 to 47 years of age) served as control subjects. The control subjects had no history of gastrointestinal disease or previous abdominal surgery. Informed consent was obtained from each patient and control subject. All patients and subjects underwent sigmoidoscopy without air insufflation. Bipolar silver-silver chloride clip electrodes (2 or 3) were attached to the colonic mucosa at 5 to 20 cm from the anus under direct vision through a sigmoidoscope. An electrode is diagrammatically illustrated in figure 1. Each bipolar electrode was connected by Teflon-insulated copper wires to a junction box containing a YI6-amp fuse. The junction box was in turn connected to a rectilinear recorder (Beckman, R411) through an A-C coupler (9806) with a time constant of 1.0 sec and a 30-Hz filter. All patients and subjects were grounded externally. Respiration was monitored by a pneumograph belt placed around the chest and connected to a transducer (Statham P231a). Intraluminal pressure was measured at the same level as each electrode. Pressure was measured using water-filled,

2 March 1976 pressure catheter I---2 c m---l H MYOELECTRIC ACTIVITY IN IRRITABLE BOWEL I I I ~ ; ~ ~ ~ ; ~ ~ ~ 1. 5 m m silver wire bipolar electrodes wires cli p electrode FIG. 1. Schematic diagram of bipolar clip electrode and pressure recording catheter. The pressure recording catheter was at the same level as that of the bipolar electrode. polyvinyl catheters (1.4 mm, inner diameter) with side orifices of 1.2 mm diameter. Each catheter was continuously perfused at 4.0 ml per hr, using an infusion pump. Pressure was transmitted to transducers (Statham P231a). All patients and subjects fasted for at least 8 hr before the study. No medications were taken for 3 days before this evaluation, and no enemas were used before sigmoidoscopy. Myoelectric recordings were begun 30 to 45 min after the removal of the sigmoidoscope. Basal recordings were performed for 90 to 180 min with the patients or subjects lying in the left lateral decubitus position. Each myoelectric recording was evaluated without knowledge of the subject's diagnosis. The records were analyzed for total recordable activity (i.e., percentage of time during which BER was present), BER frequency, and spike potential activity. Motor activity was calculated as the product of the mean amplitude of the colonic contractions multiplied by their duration. I. Statistical analysis was made with the use of Student's t-test. Results Placement and removal of the electrodes gave no adverse responses in the subjects or in the patients with irritable bowel syndrome. Myoelectric activity was recorded in all patients and subjects. In each individual, two types of BER were recorded. The major component of the BER had a frequency of approximately 6 cycles per min, while the minor component had a frequency of 3 cycles per min. Figure 2 shows the myoelectric and pressure recordings obtained in a normal subject. The BER is present at 6.0 cycles per min. No spike potential activity is present. Spontaneous contractile activitiy is absent. Figure 3 shows the myoelectric and pressure recordings obtained in a patient with the irritable bowel syndrome. The BER frequency is 3 cycles per min. Spontaneous spike potential and contractile activity are present. Myoelectric recordings in both groups showed Myoelectric and Pressure Responses in a Nor rna I Subject mv 02 1 Myoelectric (8 cm from anus) mm Hg 20e I Pressure ~ ( 8 ~ from anus) c m Respiration n " H ~ ~ m 1 W r r r ~ N ' f f 1 [ 1 N r m r r ~ r N r f f { f -I mlnute-----j FIG. 2. Myoelectric activity and pressure recorded from the rectum in a normal subject. The basic electrical rhythm was present at 6.0 cycles per min. No spike potentials or motor activity are present. Respirations are shown at bottom.

3 328 SNAPE ETAL. Vol. 70, No.3 Myoelectric and Pressure Responses in a Patient with the Irritable Bowel Syndrome mmh o O ~ i Pressure (15cm from anus) mmho o Respiration 1--' minute '--i FIG. 3. Myoelectric activity and pressure recorded from the rectum and rectosigmoid in a patient with the irritable bowel syndrome. An isolated spike potential is seen on the initial portion of the myoelectric record. Pressure activity is present at 3 contractions per min, identical with the basic electrical rhythm frequency. Respirations are shown at bottom. TABLE 1. Colonic myoelectric activity in normal controls and in patients with the irritable bowel syndrome Myoelectric activity Controls Rectum" (0-13 em from anus) IBS Controls Rectosigmoid' (14-20 em from anus) IBS % BER activity Fast BER (cycles/min) Slow BER (cycles/min) fast BER % siowber Spike potential activity per 15 min 46.0 ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± 3.5 a Each value represents the mean ± SEM for values obtained in 10 normal subjects and in 12 patients with the irritable bowel syndrome. b Each value represents the mean ± SEM for values obtained in 7 normal subjects and in 5 patients with the irritable bowel syndrome. either type of BER or an isoelectric record. Myoelectric activity varied spontaneously between the two basic types of BER and the isoelectric periods. Isoelectric periods occurred despite continued attachment of the electrodes to the bowel wall. Table 1 lists the indexes of myoelectric activity for all subjects and patients with the irritable bowel syndrome. Data are tabulated on the basis of the site of recording. The total recordable BER was similar in normal subjects and in patients with the irritable bowel syndrome in both the rectum and rectosigmoid (P > 0.05). The remainder of the total recording periods in each group was isoelectric. The mean frequency of each type of BER was similar in the two groups (P> 0.05). Also, the spontaneous spike potential activity was similar in both groups (P> 0.05). The major distinction in myoelectric activity in normal subjects and in patients with the irritable bowel syndrome was the striking difference in the percentage of time occupied by each of the two types of BER. In patients with the irritable bowel syndrome, the slowerfrequency BER was recorded for a greater proportion of time in both the rectum and rectosigmoid (P < 0.001). This difference is better shown in figure 4 which illustrates the percentage of time occupied by the 3 cycle- Rectum Rectosig moid -100%- -100% ~ I -20- I t! W ~ Normal Irritable Normal Irrllable Bowel Bowel FIG. 4. Slow-frequency basic electrical rhythm (BER) expressed as a percentage of total BER activity in normal subjects and in patients with the irritable bowel syndrome. Each point represents the value obtained in a given individual. The percentage (mean ± SEM) of slow-frequency BER is shown for values obtained both in the rectum and rectosigmoid. Patients with the irritable bowel syndrome showed a greater percentage of slow-frequency BER in both the rectum and rectosigmoid (P < 0.(01).

4 March 1976 MYOELECTRIC ACTIVITY IN IRRITABLE BOWEL 329 per min BER in each patient and subject. Data are expressed as a percentage of total recorded BER activity in each individual. Patients with the irritable bowel syndrome had a significantly greater percentage of the recorded BER occurring at the slower frequency in both the rectum and the rectosigmoid. Basal motor activity recorded using the open-tipped catheters showed no significant difference between the normal subjects and patients with the irritable bowel syndrome. Similarly, basal motor activity did not differ significantly during the two BER frequencies. In patients with the irritable bowel syndrome, no difference in myoelectric activity was demonstrated in patients with different types of symptoms or in patients with longer duration of symptoms. Patient age or sex did not seem to influence myoelectric parameters. Discussion The recording of colonic myoelectric activity provides an index of smooth muscle function and its level of excitation as measured by spike potential activity. The origin of the colonic BER is still under investigation. In cats, the BER is generated in the circular muscle layer, whereas in the dog and in man, the BER seems to originate in the longitudinal muscle The BER of adjacent areas of the colon is thought to be linked through a series of coupled relaxation oscillators which act as an integrating mechanism for the control of colonic motor function However, the mechanism by which the c o l ober n i ~ regulates colonic motor activity is more complex than in the small intestine. In contrast with the small bowel, the colonic BER frequency in cats is considerably slower and increases aborally Indirect evidence that colonic BER serves art integrating, or control function in the colon is based upon animal studies. In cats with idiopathic diarrhea 10 or diarrhea induced by castor oil, 11 there is a marked dysrhythmia of BER. Several lines of evidence suggest that the irritable bowel syndrome is a colonic motor disturbance. First, colonic motor activity is increased in patients with the irritable bowel syndrome in response to eating,3 cholecystokinin,4 emotional stress,2 or drugs such as prostigmine. 5 Second, increased colonic pressure produced endogenously by the stimuli noted above, correlated closely with abdominal pain observed in these patients.' Third, patients with the irritable bowel syndrom seem to have greater probability of developing colonic diverticula,18 another disorder attributed to colonic motor dysfunction. 19 Based upon the suggestion that myoelectric activity is an important index of intrinsic colonic function and that the irritable bowel syndrome is principally a motor disturbance of the large intestine, we compared myoelectric activity in normal subjects and in patients with the irritable bowel syndrome. Previous studies in man and in animals have shown that the BER is not present at all times. 6-8 The BER may disappear completely, leaving only an isoelectric recording. There are two possible explanations for this observation in man. First, the suction electrode may have become detached. Second, true alterations in colonic oscillators may have been responsible for the isoelectric period. In the present study, the attachment of the clip electrode was confirmed by repeat sigmoidoscopy. Since the isoelectric periods occurred during attachment of the electrode, the isoelectric periods were most likely due to oscillator interference. In a previous study in man, the BER was demonstrated to occur at two frequencies. 8 The major component was at approximately 6 cycles per min, while the minor component was at approximately 3 cycles per min. Individuals could show either frequency BER or an isoelectric state. These findings in normal subjects were confirmed in this study. The major new observation in this study was in patients with the irritable bowel syndrome. In these patients, an increased percentage of the BER was at the 3 cycles per min frequency. This difference was observed in the rectum and rectosigmoid. The etiology of the altered basal BER in the irritable bowel syndrome is not known. In vitro, the BER may be decreased by parasympathomimetics, a-adrenergic agents, serotonin, or morphine. 20 However, the change in frequency in response to these agents was not marked, and did not achieve the frequency of 3 cycles per min. In man, the only agent shown to increase the percentage of 3-cycles-per-min BER was intravenous pentagastrin. 8 Although the BER may be altered by pentagastrin in man, it is uncertain whether the changes seen in patients with irritable bowel syndrome are related to intrinsic myogenic factors or extrinsic factors acting upon the muscle. The effect of gastrin on colonic motor activity in man is unclear because opposite findings have been reported The recording of an altered biopotential in the colon in patients with the irritable bowel syndrome still leaves a major question to be resolved. Is the increased percentage of 3 cycles per min BER activity observed in the colon related to the clinical manifestation of the irritable bowel syndr'jme? The change in BER has not been causally related to either abdominal pain or disordered colonic transport. However, one major earlier observation in man may serve to answer this problem. It has been shown that the colonic contractile activity in response to hormonal stimulation differs markedly, dependent upon the BER at the time of stimulation. 8 Colonic contractile activity in response to pentagastrin can be elicited only when the BER is in the 3 cycles per min range. Inasmuch as many studies suggest that the irritable bowel syndrome can be best characterized by the abnormal colonic contractile response to certain stimuli, it may be that this altered responsiveness is related to the low-frequency BER. The low-frequency BER may serve as the underlying substrate upon which other factors act to elicit symptoms and to alter colonic transport. Thus, the irritable bowel syndrome may be due to a combination of certain emotional, hormonal, or neural factors acting upon a colon which has the intrinsic ability to respond to these stimuli. Further studies are required to support this hypothesis.

5 330 SNAPE ETAL. Vol. 70, No.3 The present study failed to show a difference in basal colonic contractile activity in normal subjects and in patients with the irritable bowel syndrome. Previous studies of basal colonic motor function have shown either increased or normal activity in symptomatic patients. 23,24 With specific stimuli, either hormonal or emotiond, increased motor responses can be elicited in patients with irritable bowel syndrome. The myoelectric recordings suggest that even under conditions where motor activity is similar to that in normal subjects patients with the irritable bowel syndrome have a significant difference in the properties of the distal large intestine. REFERENCES 1. Almy TP: Digestive disease as a national problem. II. A white paper by the American Gastroenterological Association. Gastroenterology 53: "33, Chaudhary NA, Truelove SC: Human colonic motility: a comparative study of normal subjects, patients with ulcerative colitis, and patients with the irritable colon syndrome. III. EtIect of emotions. Gastroenterology 40:27-36, Connell AM, Avery Jones F, Rowlands EN: Motility of the pelvic colon. IV: Abdominal pain associated with colonic hypermotility after meals. Gut 6: , Harvey RF, Read AE: Effect of cholecystokinin on colonic motility and symptoms in patients with the irritable-bowel syndrome. Lancet 1: 1-3, Chaudhary NA, Truelove SC: Human colonic motility: a comparative s t l of ~ dnormal y subjects, patients with ulcerative colitis, and patients with the irritable colon syndrome. II. The effect of prostigmine. Gastroenterology 40: 18-26, Couturier D, Roze C, Couturier-Turpin MA, et al: Electromyography of the colon in situ. An experimental study in man and in the rabbit. Gastroenterology 56: , Provenzale L, Pisano M: Methods for recording electrical activity of the human colon in vivo. Am J Dig Dis 16: , Taylor I, Duthie HL, Smallwood R, et al: The effect of stimulation on the myoelectric activity of the rectosigmoid in man. Gut 15: , Wienbeck M, Christensen J, Weisbrodt NW: Electromyography of the colon in the unanesthetized cat. Am J Dig Dis 17: , Christensen J, Weisbrodt NW, Hauser RL: Electrical slow wave of the proximal colon of the cat in diarrhea. Gastroenterology 62: , Christensen J, Freeman BW: Circular muscle electromyogram in the cat colon: Local effect of sodium ricinoleate. Gastroenterology 63: , Connell AM: The motility of the pelvic colon. I. Motility in normals and in patients with asymptomatic duodenal ulcer. Gut 2:l75-186, Caprilli R, Grori L: Origin, transmission and ionic dependence of colonic electrical slow waves. Scand J Gastroenterol 7:65-74, Vanasin B, Ustach TJ, Schuster MM: Electrical and motor activity of human and dog colon in vitro. Johns Hopkins Med J 134: , Christensen J, Hauser RL: Longitudinal axial coupling of slow waves in proximal cat colon. Am J Physiol 221: , Christensen J, Hauser RL: Circumferential coupling of electric slow waves in circular muscle of cat colon. Am J Physiol 221: , Christensen J, Anuras S, Hauser RL: Migratory spike burst and electrical slow waves in the cat colon: effects of sectioning. Gastroenterology 66: , Havia T, Manner R: The irrita ble colon syndrome. Acta Chir Scand 137: , Painter NS, Truelove SC: The intraluminal pressure patterns in diverticulosis of the colon. Gut 5: , Wienbeck M, Christensen J: Effects of some drugs on electrical activity of the isolated colon of the cat. Gastroenterology 61: , Logan CJH, Connell AM: The effect of a synthetic gastrin-like pentapeptide (ICI 50, 123) on intestinal motility in man. Lancet 1: , Misiewicz JJ, Waller SL, Holdstock DJ: Gastrointestinal motility and gastric secretion during intravenous infusion of gastrin II. Gut 10: , Chaudhary NA, Truelove SC: Human colonic motility: a comparative study of normal subjects, patients with ulcerative colitis, and patients with the irritable colon syndrome. 1. Resting patterns of motility. Gastroenterology 40: 1-17, Bloom AA, LoPresti P, Farrar.JT: Motility of the intact human colon. Gastroenterology 54: , 1968

Official Publication of the American Gastroe1lterological Association

GASTROENTEROLOGY@ Official Publication of the American Gastroe1lterological Association COPYRIGHT 1977 THE WILLIAMS & WILKINS Co. Vol. 72 March 1977 Number 3 ALIMENTARY TRACT EVIDENCE THAT ABNORMAL MYOELECTRICAL